Docking and scoring with alternative side-chain conformations

2009 ◽  
Vol 74 (3) ◽  
pp. 712-726 ◽  
Author(s):  
Christoph Hartmann ◽  
Iris Antes ◽  
Thomas Lengauer
Keyword(s):  
Side Chain ◽  
Docking And Scoring ◽  
Chain Conformations

Stereospecific Association of C-20 Epimers of 3β-Hydroxy-16-oxo-24-nor-17-azachol-5-eno-23-nitryle

1997 ◽  
Vol 52 (6) ◽  
pp. 749-756
Author(s):  
Zofia Plesnar ◽  
Stanisław Malanowski ◽  
Zenon Lotowski ◽  
Jacek W. Morzycki ◽  
Jadwiga Frelek ◽  
...  
Keyword(s):  
Proton Nuclear Magnetic Resonance ◽  
Side Chain ◽  
Water Molecules ◽  
Carbonyl Groups ◽  
Nmr Data ◽  
Molecular Modelling Studies ◽  
Modelling Studies ◽  
Lactam Carbonyl ◽  
Self Association ◽  
Chain Conformations

Abstract The cryoscopic measurements show that title compounds are strongly associated in CHCl3 solutions. The association of the 20 R epimer is distinctly less pronounced than that of the 20 S epipmer. Self-association of the 20 S epimer leads to the formation of very large com­plexes. The 20 R epimer forms associates via water molecules. The dissimilarity may be ex­plained in terms of different accessibility of the lactam carbonyl groups in the two epimers for the association. It is proposed that the association process is controlled by the configura­tion at the carbon atom C(20) and conformation around the C(20)-C(22) bond. Populations of side chain conformations of both epimers were determined by means of proton nuclear magnetic resonance. It was found for the 20 R epimer that the t and the -g rotamers are almost equally populated, and the rotamer +g is excluded. For the 20 S epimer the +g rotamer predominates over the t one, and the -g rotamer is excluded. The NMR data are fully consistent with the results of the molecular modelling studies.

The influence of side-chain conformations on the phase behavior of bottlebrush block polymers

Soft Matter ◽  
2020 ◽  
Vol 16 (34) ◽  
pp. 8047-8056
Author(s):  
Yuguo Chen ◽  
Xinghua Zhang ◽  
Ying Jiang
Keyword(s):  
Self Assembly ◽  
Side Chain ◽  
Chain Model ◽  
Block Polymers ◽  
Consistent Field ◽  
Self Consistent Field ◽  
Self Consistent Field Theory ◽  
Assembly Behavior ◽  
Wormlike Chain Model ◽  
Chain Conformations

A self-consistent field theory based on the wormlike chain model is implemented in the investigation of the self-assembly behavior of bottlebrush block polymers in the formation of a lamellar phase.

scholarly journals Computational Feasibility of an Exhaustive Search of Side-Chain Conformations in Protein-Protein Docking

2018 ◽  
Vol 39 (24) ◽  
pp. 2012-2021 ◽  
Author(s):  
Taras Dauzhenka ◽  
Petras J. Kundrotas ◽  
Ilya A. Vakser
Keyword(s):  
Protein Docking ◽  
Exhaustive Search ◽  
Side Chain ◽  
Chain Conformations

Protein–Protein Docking with Simultaneous Optimization of Rigid-body Displacement and Side-chain Conformations

2003 ◽  
Vol 331 (1) ◽  
pp. 281-299 ◽  
Author(s):  
Jeffrey J. Gray ◽  
Stewart Moughon ◽  
Chu Wang ◽  
Ora Schueler-Furman ◽  
Brian Kuhlman ◽  
...  
Keyword(s):  
Rigid Body ◽  
Protein Docking ◽  
Simultaneous Optimization ◽  
Side Chain ◽  
Rigid Body Displacement ◽  
Chain Conformations

scholarly journals Collective repacking reveals that the structures of protein cores are uniquely specified by steric repulsive interactions

2017 ◽  
Vol 30 (5) ◽  
pp. 387-394 ◽  
Author(s):  
J.C. Gaines ◽  
A. Virrueta ◽  
D.A. Buch ◽  
S.J. Fleishman ◽  
C.S. O'Hern ◽  
...  
Keyword(s):  
Hard Sphere ◽  
Protein Structures ◽  
Standard Test ◽  
Protein Modeling ◽  
Side Chain ◽  
Hard Sphere Model ◽  
Sphere Model ◽  
Modeling Software ◽  
High Prediction ◽  
Chain Conformations

Abstract Protein core repacking is a standard test of protein modeling software. A recent study of six different modeling software packages showed that they are more successful at predicting side chain conformations of core compared to surface residues. All the modeling software tested have multicomponent energy functions, typically including contributions from solvation, electrostatics, hydrogen bonding and Lennard–Jones interactions in addition to statistical terms based on observed protein structures. We investigated to what extent a simplified energy function that includes only stereochemical constraints and repulsive hard-sphere interactions can correctly repack protein cores. For single residue and collective repacking, the hard-sphere model accurately recapitulates the observed side chain conformations for Ile, Leu, Phe, Thr, Trp, Tyr and Val. This result shows that there are no alternative, sterically allowed side chain conformations of core residues. Analysis of the same set of protein cores using the Rosetta software suite revealed that the hard-sphere model and Rosetta perform equally well on Ile, Leu, Phe, Thr and Val; the hard-sphere model performs better on Trp and Tyr and Rosetta performs better on Ser. We conclude that the high prediction accuracy in protein cores obtained by protein modeling software and our simplified hard-sphere approach reflects the high density of protein cores and dominance of steric repulsion.

scholarly journals His224 Alters the R2 Drug Binding Site and Phe218 Influences the Catalytic Efficiency of the Metallo-β-Lactamase VIM-7

2014 ◽  
Vol 58 (8) ◽  
pp. 4826-4836 ◽  
Author(s):  
Hanna-Kirsti S. Leiros ◽  
Susann Skagseth ◽  
Kine Susann Waade Edvardsen ◽  
Marit Sjo Lorentzen ◽  
Gro Elin Kjæreng Bjerga ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Active Site ◽  
Pathogenic Bacteria ◽  
Catalytic Efficiency ◽  
Drug Binding ◽  
Side Chain ◽  
Wild Type ◽  
Drug Binding Site ◽  
Chain Conformations ◽  
Positively Charged

ABSTRACTMetallo-β-lactamases (MBLs) are the causative mechanism for resistance to β-lactams, including carbapenems, in many Gram-negative pathogenic bacteria. One important family of MBLs is the Verona integron-encoded MBLs (VIM). In this study, the importance of residues Asp120, Phe218, and His224 in the most divergent VIM variant, VIM-7, was investigated to better understand the roles of these residues in VIM enzymes through mutations, enzyme kinetics, crystal structures, thermostability, and docking experiments. The tVIM-7-D120A mutant with a tobacco etch virus (TEV) cleavage site was enzymatically inactive, and its structure showed the presence of only the Zn1 ion. The mutant was less thermostable, with a melting temperature (Tm) of 48.5°C, compared to 55.3°C for the wild-type tVIM-7. In the F218Y mutant, a hydrogen bonding cluster was established involving residues Asn70, Asp84, and Arg121. The tVIM-7-F218Y mutant had enhanced activity compared to wild-type tVIM-7, and a slightly higherTm(57.1°C) was observed, most likely due to the hydrogen bonding cluster. Furthermore, the introduction of two additional hydrogen bonds adjacent to the active site in the tVIM-7-H224Y mutant gave a higher thermostability (Tm, 62.9°C) and increased enzymatic activity compared to those of the wild-type tVIM-7. Docking of ceftazidime in to the active site of tVIM-7, tVIM-7-H224Y, and VIM-7-F218Y revealed that the side-chain conformations of residue 224 and Arg228 in the L3 loop and Tyr67 in the L1 loop all influence possible substrate binding conformations. In conclusion, the residue composition of the L3 loop, as shown with the single H224Y mutation, is important for activity particularly toward the positively charged cephalosporins like cefepime and ceftazidime.

Sign in / Sign up

Export Citation Format

Share Document